The primary goal of this project is to develop microdialysis sampling methods and associated analytical techniques to study gastric ulcers. These techniques will then be used in a comparative study of ulcers induced by Heliobacter pylori and by nonsteroidal anti-inflammatory drugs (NSAIDs). The target analytes in this system include histamine, bicarbonate/pH, N-acetylneuraminic acid (NANA), nitric oxide (NO) and prostaglandins. These compounds play a direct role in ulcer formation, serve a protective role, or are biomarkers for tissue status. Microdialysis sampling will form the basis for these studies and provide capabilities not previously available for studying ulcerated and healthy gastric tissue. Where previously, several animals had to be sacrificed to collect tissue for examination at each time point, microdialysis sampling provides for continuous sampling from the gastric tissue of each experimental animal over extended times. In addition, by implanting microdialysis probes at more than one point in the stomach, both healthy and ulcerated tissue can be studied in the same animal. The project will proceed in three stages. In the first stage, cell culture models will be utilized in vitro. In this manner specific cells lines can be studied in isolation. In the second stage of this project, excised stomach tissue will be used as a model system. Gastric ulcers will be induced by ethanol, acetic acid, indomethacin, and H. pylori. The stomach will then be excised and opened along the greater curvature for in vitro investigation using microdialysis sampling. Microdialysis probes will then be placed into ulcerated and healthy tissue. The final stage of this project will be to examine the healthy and ulcerated stomach tissue in vivo using microdialysis sampling. These methods will then be used in a comparative study of ulcers induced by H. pylori and NSAIDs. In particular, the role of mucus disruption versus acid efflux will be investigated. By continually monitoring the rate of mucus secretion versus acid secretion as a function time, the relative importance of these to processes in ulceration by the various inducers can be determined. This knowledge will aid in the development of advanced preventative and remedial treatments for ulcers resulting from different inducing agents.